Muranen, Taru A., Greco, Dario ORCID: 0000-0001-9195-9003, Blomqvist, Carl ORCID: 0000-0003-3041-1938, Aittomaki, Kristiina, Khan, Sofia ORCID: 0000-0003-4185-8882, Hogervorst, Frans, Verhoef, Senno, Pharoah, Paul D. P., Dunning, Alison M., Shah, Mitul, Luben, Robert, Bojesen, Stig E., Nordestgaard, Borge G., Schoemaker, Minouk ORCID: 0000-0001-8403-2234, Swerdlow, Anthony ORCID: 0000-0001-5550-4159, Garcia-Closas, Montserrat, Figueroa, Jonine, Doerk, Thilo, Bogdanova, Natalia V., Hall, Per, Li, Jingmei ORCID: 0000-0001-8587-7511, Khusnutdinova, Elza, Bermisheva, Marina, Kristensen, Vessela, Borresen-Dale, Anne-Lise, Peto, Julian, Silva, Isabel dos Santos, Couch, Fergus J., Olson, Janet E., Hillemans, Peter, Park-Simon, Tjoung-Won, Brauch, Hiltrud ORCID: 0000-0001-7531-2736, Hamann, Ute, Burwinkel, Barbara, Marme, Frederik, Meindl, Alfons, Schmutzler, Rita K., Cox, Angela ORCID: 0000-0002-5138-1099, Cross, Simon S., Sawyer, Elinor J., Tomlinson, Ian, Lambrechts, Diether ORCID: 0000-0002-3429-302X, Moisse, Matthieu ORCID: 0000-0001-8880-9311, Lindblom, Annika, Margolin, Sara, Hollestelle, Antoinette, Martens, John W. M., Fasching, Peter A., Beckmann, Matthias W., Andrulis, Irene L., Knight, Julia A., Anton-Culver, Hoda, Ziogas, Argyrios, Giles, Graham G., Milne, Roger L., Brenner, Hermann ORCID: 0000-0002-6129-1572, Arndt, Volker ORCID: 0000-0001-9320-8684, Mannermaa, Arto, Kosma, Veli-Matti, Chang-Claude, Jenny, Rudolph, Anja, Devilee, Peter ORCID: 0000-0002-8023-2009, Seynaeve, Caroline, Hopper, John L., Southey, Melissa C., John, Esther M., Whittemore, Alice S., Bolla, Manjeet K., Wang, Qin, Michailidou, Kyriaki ORCID: 0000-0001-7065-1237, Dennis, Joe, Easton, Douglas F., Schmidt, Marjanka K. and Nevanlinna, Heli (2017). Genetic modifiers of CHEK2*1100delC-associated breast cancer risk. Genet. Med., 19 (5). S. 599 - 604. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

Full text not available from this repository.

Abstract

Purpose: CHEK2*1100delC is a founder variant in European populations that confers a two-to threefold increased risk of breast cancer (BC). Epidemiologic and family studies have suggested that the risk associated with CHEK2*1100delC is modified by other genetic factors in a multiplicative fashion. We have investigated this empirically using data from the Breast Cancer Association Consortium (BCAC). Methods: Using genotype data from 39,139 (624 1100delC carriers) BC patients and 40,063 (224) healthy controls from 32 BCAC studies, we analyzed the combined risk effects of CHEK2*1100delC and 77 common variants in terms of a polygenic risk score (PRS) and pairwise interaction. Results: The PRS conferred odds ratios (OR) of 1.59 (95% CI: 1.212.09) per standard deviation for BC for CHEK2*1100delC carriers and 1.58 (1.55-1.62) for noncarriers. No evidence of deviation from the multiplicative model was found. The OR for the highest quintile of the PRS was 2.03 (0.86-4.78) for CHEK2*1100delC carriers, placing them in the high risk category according to UK NICE guidelines. The OR for the lowest quintile was 0.52 (0.16-1.74), indicating a lifetime risk close to the population average. Conclusion: Our results confirm the multiplicative nature of risk effects conferred by CHEK2*1100delC and the common susceptibility variants. Furthermore, the PRS could identify carriers at a high lifetime risk for clinical actions.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Muranen, Taru A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Greco, DarioUNSPECIFIEDorcid.org/0000-0001-9195-9003UNSPECIFIED
Blomqvist, CarlUNSPECIFIEDorcid.org/0000-0003-3041-1938UNSPECIFIED
Aittomaki, KristiinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Khan, SofiaUNSPECIFIEDorcid.org/0000-0003-4185-8882UNSPECIFIED
Hogervorst, FransUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Verhoef, SennoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Pharoah, Paul D. P.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Dunning, Alison M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Shah, MitulUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Luben, RobertUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bojesen, Stig E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nordestgaard, Borge G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schoemaker, MinoukUNSPECIFIEDorcid.org/0000-0001-8403-2234UNSPECIFIED
Swerdlow, AnthonyUNSPECIFIEDorcid.org/0000-0001-5550-4159UNSPECIFIED
Garcia-Closas, MontserratUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Figueroa, JonineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Doerk, ThiloUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bogdanova, Natalia V.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hall, PerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Li, JingmeiUNSPECIFIEDorcid.org/0000-0001-8587-7511UNSPECIFIED
Khusnutdinova, ElzaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bermisheva, MarinaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kristensen, VesselaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Borresen-Dale, Anne-LiseUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Peto, JulianUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Silva, Isabel dos SantosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Couch, Fergus J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Olson, Janet E.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hillemans, PeterUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Park-Simon, Tjoung-WonUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brauch, HiltrudUNSPECIFIEDorcid.org/0000-0001-7531-2736UNSPECIFIED
Hamann, UteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burwinkel, BarbaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Marme, FrederikUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Meindl, AlfonsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmutzler, Rita K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Cox, AngelaUNSPECIFIEDorcid.org/0000-0002-5138-1099UNSPECIFIED
Cross, Simon S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Sawyer, Elinor J.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Tomlinson, IanUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lambrechts, DietherUNSPECIFIEDorcid.org/0000-0002-3429-302XUNSPECIFIED
Moisse, MatthieuUNSPECIFIEDorcid.org/0000-0001-8880-9311UNSPECIFIED
Lindblom, AnnikaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Margolin, SaraUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hollestelle, AntoinetteUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Martens, John W. M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Fasching, Peter A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Beckmann, Matthias W.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Andrulis, Irene L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Knight, Julia A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Anton-Culver, HodaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ziogas, ArgyriosUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Giles, Graham G.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Milne, Roger L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Brenner, HermannUNSPECIFIEDorcid.org/0000-0002-6129-1572UNSPECIFIED
Arndt, VolkerUNSPECIFIEDorcid.org/0000-0001-9320-8684UNSPECIFIED
Mannermaa, ArtoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Kosma, Veli-MattiUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Chang-Claude, JennyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Rudolph, AnjaUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Devilee, PeterUNSPECIFIEDorcid.org/0000-0002-8023-2009UNSPECIFIED
Seynaeve, CarolineUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Hopper, John L.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Southey, Melissa C.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
John, Esther M.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Whittemore, Alice S.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Bolla, Manjeet K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Wang, QinUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Michailidou, KyriakiUNSPECIFIEDorcid.org/0000-0001-7065-1237UNSPECIFIED
Dennis, JoeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Easton, Douglas F.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Schmidt, Marjanka K.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nevanlinna, HeliUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-233209
DOI: 10.1038/gim.2016.147
Journal or Publication Title: Genet. Med.
Volume: 19
Number: 5
Page Range: S. 599 - 604
Date: 2017
Publisher: NATURE PUBLISHING GROUP
Place of Publication: NEW YORK
ISSN: 1530-0366
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
FAMILY-HISTORY; MUTATION; BRCA2; WOMENMultiple languages
Genetics & HeredityMultiple languages
Refereed: Yes
URI: http://kups.ub.uni-koeln.de/id/eprint/23320

Downloads

Downloads per month over past year

Altmetric

Export

Actions (login required)

View Item View Item